If pancreatitis is suspected, JANUVIA should promptly be discontinued and appropriate management should be initiated. Mechanism Of Action. Concentrations of the active intact hormones are increased by sitagliptin, thereby increasing and prolonging the action of these hormones. Januvia is an aromatic compound with a terminal polar Sitagliptin, more commonly known as Januvia, has been approved for the therapy of type 2 diabetes.Incretin hormones, Glucagon-like peptide-1 (GLP-1) and Glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day and levels are increased in response to a meal.The incretin hormones GLP-1 and GIP are released by the intestine and signal the synthesis and release of insulin from pancreatic beta-cells.Prolonged treatment of DPP-4 inhibitors has been linked to an increased risk in hypoglycemia, weight gain, as well as gastrointestinal side effects. Prolonged exposure to these hormones may increase the risk of high blood pressure, neurogenic inflammation and allergic reactions.Januvia has been linked to rheumatoid arthritis and various acute and chronic inflammatory diseases.Proteopedia is hosted by the ISPC at the Weizmann Institute of Science in Israel Patients were on a stable dose of insulin prior to enrollment with no changes in insulin dose permitted during the run-in period. Therefore, a lower dose of sulfonylurea or insulin may be required to reduce the risk of hypoglycemia.The incidence (and rate) of hypoglycemia based on all reports of symptomatic hypoglycemia were: 12.2% (0.59 episodes/patient-year) for JANUVIA 100 mg in combination with glimepiride (with or without metformin), 1.8% (0.24 episodes/patient-year) for placebo in combination with glimepiride (with or without metformin), 15.5% (1.06 episodes/patient-year) for JANUVIA 100 mg in combination with insulin (with or without metformin), and 7.8% (0.51 episodes/patient-year) for placebo in combination with insulin (with or without metformin).There have been postmarketing reports of serious hypersensitivity reactions in patients treated with JANUVIA, such as anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. Mean reductions from baseline in A1C were generally greater for patients with higher baseline A1C values. Patients experienced relief of symptoms upon discontinuation of the medication. The effect of JANUVIA on lipid endpoints was similar to placebo. Patients who were on a stable dose of metformin (≥1500 mg/day) in combination with a DPP-4 inhibitor and/or sulfonylurea but with inadequate glycemic control (A1C 7.5% to 11%) were enrolled in the study. Both treatment groups had an adjusted mean increase in body weight of 0.1 kg from baseline to Week 24. Through Week 54, the overall incidence of hypoglycemia was 3.9% in patients given add-on JANUVIA and 1.0% in patients given add-on placebo.In the 24-week, placebo-controlled factorial study of initial therapy with JANUVIA in combination with metformin, the incidence of hypoglycemia was 0.6% in patients given placebo, 0.6% in patients given JANUVIA alone, 0.8% in patients given metformin alone, and 1.6% in patients given JANUVIA in combination with metformin.In the study of JANUVIA as initial therapy with pioglitazone, one patient taking JANUVIA experienced a severe episode of hypoglycemia. Sitagliptin works to competitively inhibit the enzyme dipeptidyl peptidase 4 (DPP-4). Initial therapy with the combination of JANUVIA and metformin provided significant improvements in A1C, FPG, and 2-hour PPG compared to placebo, to metformin alone, and to JANUVIA alone (Table 8, Figure 1). Sitagliptin (Januvia) is a medication prescribed for the treatment of type 2 diabetes. Sitagliptin demonstrates selectivity for DPP-4 and does not inhibit DPP-8 or DPP-9 activity In patients with type 2 diabetes mellitus, administration of sitagliptin led to inhibition of DPP-4 enzyme activity for a 24-hour period. A total of 701 patients with type 2 diabetes participated in a 24-week, randomized, double-blind, placebo-controlled study designed to assess the efficacy of JANUVIA in combination with metformin.